Nevin Manimala

Blood Cancer J. 2021 Nov 20;11(11):183. doi: 10.1038/s41408-021-00573-6.

ABSTRACT

Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative option for many hematologic conditions and is associated with considerable morbidity and mortality. Therefore, prognostic tools are essential to navigate the complex patient, disease, donor, and transplant characteristics that differentially influence outcomes. We developed a novel, comprehensive composite prognostic tool. Using a lasso-penalized Cox regression model (n = 273), performance status, HCT-CI, refined disease-risk index (rDRI), donor and recipient CMV status, and donor age were identified as predictors of disease-free survival (DFS). The results for overall survival (OS) were similar except for recipient CMV status not being included in the model. Models were validated in an external dataset (n = 378) and resulted in a c-statistic of 0.61 and 0.62 for DFS and OS, respectively. Importantly, this tool incorporates donor age as a variable, which has an important role in HSCT outcomes. This needs to be further studied in prospective models. An easy-to-use and a web-based nomogram can be accessed here: https://allohsctsurvivalcalc.iowa.uiowa.edu/ .

PMID:34802042 | DOI:10.1038/s41408-021-00573-6

Lab Invest. 2021 Nov 20. doi: 10.1038/s41374-021-00700-8. Online ahead of print.

ABSTRACT

Brain tumors are the leading cause of cancer-related death in children. Tazemetostat is an FDA-approved enhancer of zeste homolog (EZH2) inhibitor. To determine its role in difficult-to-treat pediatric brain tumors, we examined EZH2 levels in a panel of 22 PDOX models and confirmed EZH2 mRNA over-expression in 9 GBM (34.6 ± 12.7-fold) and 11 medulloblastoma models (6.2 ± 1.7 in group 3, 6.0 ± 2.4 in group 4) accompanied by elevated H3K27me3 expression. Therapeutic efficacy was evaluated in 4 models (1 GBM, 2 medulloblastomas and 1 ATRT) via systematically administered tazemetostat (250 and 400 mg/kg, gavaged, twice daily) alone and in combination with cisplatin (5 mg/kg, i.p., twice) and/or radiation (2 Gy/day × 5 days). Compared with the untreated controls, tazemetostat significantly (P_corrected < 0.05) prolonged survival times in IC-L1115ATRT (101% at 400 mg/kg) and IC-2305GBM (32% at 250 mg/kg, 45% at 400 mg/kg) in a dose-dependent manner. The addition of tazemetostat with radiation was evaluated in 3 models, with only one [IC-1078MB (group 4)] showing a substantial, though not statistically significant, prolongation in survival compared to radiation treatment alone. Combining tazemetostat (250 mg/kg) with cisplatin was not superior to cisplatin alone in any model. Analysis of in vivo drug resistance detected predominance of EZH2-negative cells in the remnant PDOX tumors accompanied by decreased H3K27me2 and H3K27me3 expressions. These data supported the use of tazemetostat in a subset of pediatric brain tumors and suggests that EZH2-negative tumor cells may have caused therapy resistance and should be prioritized for the search of new therapeutic targets.

PMID:34802040 | DOI:10.1038/s41374-021-00700-8

Int J Obes (Lond). 2021 Nov 20. doi: 10.1038/s41366-021-01022-x. Online ahead of print.

ABSTRACT

BACKGROUND: In women, metabolic health deteriorates after menopause, and the role of physical activity (PA) in mitigating the change is not completely understood. This study investigates the changes in indicators of metabolic health around menopause and evaluates whether PA modulates these changes.

METHODS: Longitudinal data of 298 women aged 48-55 years at baseline participating in the ERMA and EsmiRs studies was used. Mean follow-up time was 3.8 (SD 0.1) years. Studied indicators of metabolic health were total and android fat mass, waist circumference, waist-to-hip ratio (WHR), systolic (SBP) and diastolic (DBP) blood pressure, blood glucose, triglycerides, serum total cholesterol, and high- (HDL-C) and low-density (LDL-C) lipoprotein cholesterol. PA was assessed by accelerometers and questionnaires. The participants were categorized into three menopausal groups: PRE-PRE (pre- or perimenopausal at both timepoints, n = 56), PRE-POST (pre- or perimenopausal at baseline, postmenopausal at follow-up, n = 149), and POST-POST (postmenopausal at both timepoints, n = 93). Analyses were carried out using linear and Poisson mixed-effect models.

RESULTS: At baseline, PA associated directly with HDL-C and inversely with LDL-C and all body adiposity variables. An increase was observed in total (B = 1.72, 95% CI [0.16, 3.28]) and android fat mass (0.26, [0.06, 0.46]), SBP (9.37, [3.34, 15.39]), and in all blood-based biomarkers in the PRE-POST group during the follow-up. The increase tended to be smaller in the PRE-PRE and POST-POST groups compared to the PRE-POST group, except for SBP. The change in PA associated inversely with the change in SBP (-2.40, [-4.34, -0.46]) and directly with the change in WHR (0.72, [0.05, 1.38]).

CONCLUSIONS: In middle-aged women, menopause may accelerate the changes in multiple indicators of metabolic health. PA associates with healthier blood lipid profile and body composition in middle-aged women but does not seem to modulate the changes in most of the studied metabolic health indicators during the menopausal transition.

PMID:34802032 | DOI:10.1038/s41366-021-01022-x

Spine (Phila Pa 1976). 2021 Nov 19. doi: 10.1097/BRS.0000000000004284. Online ahead of print.

ABSTRACT

STUDY DESIGN: Cross-sectional study.

OBJECTIVE: This study aimed to objectively evaluate spastic gait and reveal its novel characteristics via analysis of gait in patients with cervical myelopathy (CM) using the Timed Up and Go (TUG) test with a laser range sensor.

SUMMARY OF BACKGROUND DATA: Among patients with CM, spastic gait is a common diagnostic symptom; thus, objective assessments of spastic gait would be useful for the diagnosis of CM and recognition of disease status. Although spastic gait has been objectively evaluated in previous studies, the methods employed in those studies are not suitable for clinical settings.

METHODS: In total, 37 and 24 participants were recruited for a control group and CM group, respectively. CM was diagnosed by spine surgeons. We developed a laser TUG test, in which the position and velocity of both the legs were captured. The parameter values for both groups were statistically compared, and odds ratios were calculated using logistic regression analyses.

RESULTS: The total TUG test time, time to stand up, time to first step, number of steps, and trajectory error for the CM group were significantly higher than those for the control group, whereas the average velocity and average stride length for the CM group were significantly lower than those for the control group. There was a significant independent association between the total TUG test time and CM. The optimal cutoff point of the total test time for CM risk was approximately 9 seconds.

CONCLUSION: Through the use of the laser TUG test, we were able to identify characteristics of spastic gait, which leads to difficulty in standing and taking the first step, wobbling while walking, and an increased risk of falling. We found that the risk of CM was higher if the individual took longer than 9 seconds to complete the TUG test.Level of Evidence: 4.

PMID:34802028 | DOI:10.1097/BRS.0000000000004284

Spine (Phila Pa 1976). 2021 Nov 19. doi: 10.1097/BRS.0000000000004280. Online ahead of print.

ABSTRACT

STUDY DESIGN: Randomized controlled trial.

OBJECTIVE: To evaluate the efficacy of adjunctive topical tranexamic acid (tTXA) in reducing postoperative blood loss and packed red cell (PRC) transfusion in patients who underwent palliative decompressive spinal metastasis surgery for malignant epidural spinal cord compression.

SUMMARY OF BACKGROUND DATA: Palliative decompressive spinal metastasis surgery is associated with massive postoperative blood loss and increased transfusion rate. tTXA reduces blood loss in traumatic or degenerative spinal surgery; however, the role of topical TXA in decompressive spinal metastasis surgery remains controversial.

METHOD: A total of 65 patients who underwent palliative decompressive thoracolumbar spinal metastasis surgery were included in this study. In 33 patients, 1 g of tTXA (20 mL) was soaked in an absorbable gelatin sponge and placed lateral to the decompressive site. The remaining 32 patients in the control group received the same procedures with normal saline at the same volume, instead of TXA. All of the patients received standard 1 g intravenous TXA, just before initiating the operation. The primary outcome was postoperative blood loss, and the secondary outcomes were postoperative PRC transfusion and complications.

RESULTS: No differences were found in postoperative blood loss between tTXA and placebo group (P50 778 mL [IQR 347, 1,122 mL] versus P50 490 mL [IQR 295, 920 mL]; P = 0.238). The number of patients requiring postoperative PRC transfusion were quite similar in tTXA and placebo groups (PRC transfusion in 15 patients [45.45%] versus 16 patients [50%]; P = 0.585). No complications related to TXA and absorbable gelatin sponge were observed.

CONCLUSIONS: We do not recommend tTXA as an adjunctive treatment for patients undergoing decompressive spinal metastasis surgery since it does not provide additional benefit to prophylactic intravenous TXA in postoperative blood loss and transfusion rate.Level of Evidence: 2.

PMID:34802026 | DOI:10.1097/BRS.0000000000004280

J Clin Gastroenterol. 2021 Nov 22. doi: 10.1097/MCG.0000000000001642. Online ahead of print.

ABSTRACT

GOAL: The goal of this study was to determine the accuracy of Model of End-stage Liver Disease-Sodium (MELD-Na) in predicting 6-month mortality for patients listed for liver transplantation on the United Network of Organ Sharing (UNOS) waitlist.

BACKGROUND: End-stage liver disease patients underutilize hospice services despite significant morbidity and mortality associated with advanced liver disease. A well-known barrier to hospice referral is clinician uncertainty in identifying patients with an expected survival of <6 months, a requirement for a referral.

METHODS: Retrospective cross-sectional analysis was performed from UNOS data spanning February 27, 2002, to September 30, 2019. Inclusion criteria of patients aged 18 years and above, diagnosis of cirrhosis, liver transplant eligible, and listed in the UNOS database. Exclusion criteria included fulminant hepatic failure, prior history of liver transplantation, diagnosis of hepatocellular carcinoma, receipt of liver transplant in <180 days, or removal from waiting list <180 days for a reason other than death.

MEASUREMENT: Mortality by 180 days.

RESULTS: Of the 93,157 patients that met inclusion criteria, MELD-Na was calculated for all patients with sodium, total bilirubin, international normalized ratio, and creatinine available (N=79,611). The c-statistic with 95% confidence interval for MELD-Na for the predicted 6-month mortality was 0.83 (0.827-0.835). Mean MELD-Na of 28.2 was associated with ≤50% 6-month survival.

CONCLUSION: MELD-Na is an objective, quick measure that can aid providers in identifying patients with increased 6-month mortality in time-constrained settings, and a score of 28 can trigger the discussion for hospice as a means of improving value-based health care.

PMID:34802021 | DOI:10.1097/MCG.0000000000001642

Urol Int. 2021 Nov 19:1-8. doi: 10.1159/000519480. Online ahead of print.

ABSTRACT

INTRODUCTION: The study aimed to construct and validate a risk prediction model for incidence of postoperative renal failure (PORF) following radical nephrectomy and nephroureterectomy.

METHODS: The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database years 2005-2014 were used for the derivation cohort. A stepwise multivariate logistic regression analysis was conducted, and the final model was validated with an independent cohort from the ACS-NSQIP database years 2015-2017.

RESULTS: In cohort of 14,519 patients, 296 (2.0%) developed PORF. The final 9-factor model included age, gender, diabetes, hypertension, BMI, preoperative creatinine, hematocrit, platelet count, and surgical approach. Model receiver-operator curve analysis provided a C-statistic of 0.79 (0.77, 0.82; p < 0.001), and overall calibration testing R2 was 0.99. Model performance in the validation cohort provided a C-statistic of 0.79 (0.76, 0.81; p < 0.001).

CONCLUSION: PORF is a known risk factor for chronic kidney disease and cardiovascular morbidity, and is a common occurrence after unilateral kidney removal. The authors propose a robust and validated risk prediction model to aid in identification of high-risk patients and optimization of perioperative care.

PMID:34802009 | DOI:10.1159/000519480

Psychopathology. 2021 Nov 19:1-6. doi: 10.1159/000520087. Online ahead of print.

ABSTRACT

Short-lived psychotic disorders as currently listed under “acute and transient psychotic disorder,” ICD-11 Classification of Mental, Behavioural, and Neurodevelopmental Disorders, and “brief psychotic disorder,” Diagnostic and Statistical Manual of Mental Disorders (DSM-5), constitute a point of divergence in the classification of psychotic disorders between the 2 diagnostic systems, which reveals the lack of knowledge about these conditions. Whether this is due to conceptual shortcomings inherent to the categories themselves and which spill over onto research or reflects a mismatch between the diagnostic criteria used and research techniques needs clarification. This study aimed to examine conceptual issues involved in the development of the above categories and shows that little continuity exists between earlier nosological concepts such as bouffée délirante, cycloid psychosis, and reactive psychosis and modern descriptive categories used to classify short-lived psychotic disorders. It seems likely that shortcomings in terms of symptom completeness, specificity, and heterogeneity, in addition to changes in definition and diagnostic criteria in successive DSM and ICD versions, have hampered empirical research, making it difficult to enhance the understanding of these conditions and achieve a closer concordance between the 2 classificatory systems.

PMID:34802004 | DOI:10.1159/000520087

Orv Hetil. 2021 Nov 21;162(47):1891-1896. doi: 10.1556/650.2021.32271.

ABSTRACT

Összefoglaló. Bevezetés: A szédülés időskorban gyakori panasz, amely jelentősen befolyásolja az életminőséget. Háttere sok esetben multifaktoriális, egyes esetekben azonban jól meghatározott ok kimutatható. Célkitűzés: Kutatásunk célja az időskori szédülő populáció panaszainak, valamint életminőségének felmérése volt. Anyag és módszer: Kutatásunkba 36 (13 férfi, 23 nőbeteg, átlagéletkor ± SD, 72,78 év ± 4,6), Otoneurológiai Ambulanciánkon szédülés miatt vizsgált, 65 év feletti beteget vontunk be. Ők az általunk összeállított, panaszokkal és rizikófaktorokkal kapcsolatos kérdőív mellett a Dizziness Handicap Inventory-t is kitöltötték. Az utóbbi alapján meghatározható volt az életminőség-romlás, illetve annak mértéke. A statisztikai elemzést az IBM SPSS V24 szoftver segítségével végeztük, Mann-Whitney U-teszt és khi-négyzet-próba alapján. Minden esetben p<0,05 értéket tekintettünk szignifikáns különbségnek. Eredmények: A leggyakoribb diagnózisként a Ménière-betegséget, valamint a centrális vestibularis eltéréseket detektáltuk. A betegek visszajelzése alapján a szédülés volt a legdominánsabb tünet, amely a leggyakrabban órákig, illetve napokig tartott, és fele arányban volt forgó jellegű. Emellett a fülzúgás, a halláscsökkenés, valamint a vegetatív tünetek is dominánsak voltak. A leggyakoribb társbetegségek közül gyakoriságuk miatt kiemelendők a mozgásszervi, illetve szemészeti eltérések, a hypertonia, valamint a pszichiátriai betegségek. A betegek 77,8%-a jelzett valamilyen mértékű életminőség-romlást, és kiemelendő, hogy 30%-uk a súlyos kategóriába esett. A Dizziness Handicap Inventory kérdőívek alapján a fizikális, funkcionális, valamint emocionális részpontszámok hasonló értéket mutattak. Következtetés: Az időskori szédülés lényeges a beteg romló életminősége szempontjából. A társuló komorbiditások mellett a háttérben álló vestibularis eltérések kizárása, illetve diagnosztizálása fontos feladat. Ennek függvényében tervezhető a terápia, amely kapcsán a kísérő tünetekre is fontos hangsúlyt fektetni. Így az érintett betegek életminősége javítható. Orv Hetil. 2021; 162(47): 1891-1896.

INTRODUCTION: Vertigo is a common complaint in elderly, which has significant influence on the patients’ quality of life. In many cases its background is complex, although, in some cases specific diagnosis can be made.

OBJECTIVE: Our study aimed to analyze the symptoms and quality of life of old-age vertiginous population.

MATERIAL AND METHOD: 36 patients (13 males, 23 females, mean age ± SD, 72.78 years ± 4.6) over 65 years, examined due to vertigo at our Neurotologic Department, were enrolled. A questionnaire including questions regarding the symptoms, risk factors, along with the Dizziness Handicap Inventory was used. Statistical analysis was carried out using IBM SPSS V24 software. Mann-Whitney U and chi square tests were used. Statistical significance was defined as p<0.05.

RESULTS: Ménière’s disease and central vestibular disorders were found as the most frequent diagnoses. Vertigo was the most tormenting symptom, which usually lasted for hours or days, and was defined as rotatory in 50%. Tinnitus, hearing loss and vegetative symptoms were also dominant. The most frequent comorbidities were musculoskeletal disorders, hypertension, ophthalmological diseases and psychiatric disorders. 77.8% of the patients have reported worsened quality of life, of which 30% was detected as severe. Based on the Dizziness Handicap Inventory, physical, functional and emotional scores showed similar results.

CONCLUSION: Vertigo in elderly is important due to its influence on patients’ quality of life. Besides comorbidities, the diagnosis of vestibular pathologies is of great importance. Therefore, therapy planning is possible, and patients’ quality of life can be improved. Orv Hetil. 2021; 162(47): 1891-1896.

PMID:34801982 | DOI:10.1556/650.2021.32271

Oral Oncol. 2021 Nov 18;123:105626. doi: 10.1016/j.oraloncology.2021.105626. Online ahead of print.

ABSTRACT

OBJECTIVES: Timely administration of postoperative radiation therapy (PORT) impacts oncologic outcomes in resected squamous cell carcinomas of the head and neck. Salivary gland cancers (SGCs) are uncommon, and timing of PORT has not been extensively explored. We aimed to determine if the interval between surgery and PORT impacts outcomes in SGCs.

MATERIALS AND METHODS: This is a retrospective study of patients with SGCs who underwent curative intent surgical resection followed by adjuvant PORT. Locoregional recurrence free survival (LRFS), disease free survival (DFS), and overall survival (OS) were estimated using the Kaplan Meier method. A multivariate analysis explored the association between demographics, tumor characteristics, and PORT timing with oncologic outcomes using a stepwise Cox proportional hazards model.

RESULTS: 180 eligible patients were identified. The median time to PORT start was 61 (range 8-121) days. 169 (93.5%) of patients received neutron radiation. With a median follow up of 8.2 years in surviving patients, the 10-year OS and LRFS estimates were 61% and 53%. In a multivariate analysis, nodal involvement, histologic grade, and age at diagnosis were associated with OS, while nodal involvement, tumor size, and age at diagnosis were associated with LRFS and DFS. Time to PORT start or completion was not statistically associated with survival outcomes.

CONCLUSION: SGC patients who underwent surgery in our tertiary institution received PORT within a median of 61 days after surgery. With long term follow up, PORT timing in this retrospective series was not associated with worse oncologic outcomes, and support timely administration of PORT.

PMID:34801976 | DOI:10.1016/j.oraloncology.2021.105626